Synovial Sarcoma Preclinical Modeling: Integrating Transgenic Mouse Models and Patient-Derived Models for Translational Research
Synovial sarcomas (SyS) are rare malignant tumors predominantly affecting children, adolescents, and young adults. The genetic hallmark of SyS is the t(X;18) translocation encoding the SS18-SSX fusion gene. The fusion protein interacts with both the BAF enhancer and polycomb repressor complexes, and...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-01-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/3/588 |
| _version_ | 1797625016825675776 |
|---|---|
| author | Lorena Landuzzi Francesca Ruzzi Pier-Luigi Lollini Katia Scotlandi |
| author_facet | Lorena Landuzzi Francesca Ruzzi Pier-Luigi Lollini Katia Scotlandi |
| author_sort | Lorena Landuzzi |
| collection | DOAJ |
| description | Synovial sarcomas (SyS) are rare malignant tumors predominantly affecting children, adolescents, and young adults. The genetic hallmark of SyS is the t(X;18) translocation encoding the SS18-SSX fusion gene. The fusion protein interacts with both the BAF enhancer and polycomb repressor complexes, and either activates or represses target gene transcription, resulting in genome-wide epigenetic perturbations and altered gene expression. Several experimental in in vivo models, including conditional transgenic mouse models expressing the SS18-SSX fusion protein and spontaneously developing SyS, are available. In addition, patient-derived xenografts have been estab-lished in immunodeficient mice, faithfully reproducing the complex clinical heterogeneity. This review focuses on the main molecular features of SyS and the related preclinical in vivo and in vitro models. We will analyze the different conditional SyS mouse models that, after combination with some of the few other recurrent alterations, such as gains in BCL2, Wnt-β-catenin signaling, FGFR family, or loss of PTEN and SMARCB1, have provided additional insight into the mechanisms of synovial sarcomagenesis. The recent advancements in the understanding of SyS biology and improvements in preclinical modeling pave the way to the development of new epigenetic drugs and immunotherapeutic approaches conducive to new treatment options. |
| first_indexed | 2024-03-11T09:50:52Z |
| format | Article |
| id | doaj.art-3bbf41d763f04e64a5de3c24cd4e8306 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T09:50:52Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-3bbf41d763f04e64a5de3c24cd4e83062023-11-16T16:14:21ZengMDPI AGCancers2072-66942023-01-0115358810.3390/cancers15030588Synovial Sarcoma Preclinical Modeling: Integrating Transgenic Mouse Models and Patient-Derived Models for Translational ResearchLorena Landuzzi0Francesca Ruzzi1Pier-Luigi Lollini2Katia Scotlandi3Experimental Oncology Laboratory, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalyLaboratory of Immunology and Biology of Metastasis, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, ItalyLaboratory of Immunology and Biology of Metastasis, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, ItalyExperimental Oncology Laboratory, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalySynovial sarcomas (SyS) are rare malignant tumors predominantly affecting children, adolescents, and young adults. The genetic hallmark of SyS is the t(X;18) translocation encoding the SS18-SSX fusion gene. The fusion protein interacts with both the BAF enhancer and polycomb repressor complexes, and either activates or represses target gene transcription, resulting in genome-wide epigenetic perturbations and altered gene expression. Several experimental in in vivo models, including conditional transgenic mouse models expressing the SS18-SSX fusion protein and spontaneously developing SyS, are available. In addition, patient-derived xenografts have been estab-lished in immunodeficient mice, faithfully reproducing the complex clinical heterogeneity. This review focuses on the main molecular features of SyS and the related preclinical in vivo and in vitro models. We will analyze the different conditional SyS mouse models that, after combination with some of the few other recurrent alterations, such as gains in BCL2, Wnt-β-catenin signaling, FGFR family, or loss of PTEN and SMARCB1, have provided additional insight into the mechanisms of synovial sarcomagenesis. The recent advancements in the understanding of SyS biology and improvements in preclinical modeling pave the way to the development of new epigenetic drugs and immunotherapeutic approaches conducive to new treatment options.https://www.mdpi.com/2072-6694/15/3/588synovial sarcomaconditional mouse modelspatient-derived xenografts (PDX)epigenetic drugsimmunotherapy |
| spellingShingle | Lorena Landuzzi Francesca Ruzzi Pier-Luigi Lollini Katia Scotlandi Synovial Sarcoma Preclinical Modeling: Integrating Transgenic Mouse Models and Patient-Derived Models for Translational Research Cancers synovial sarcoma conditional mouse models patient-derived xenografts (PDX) epigenetic drugs immunotherapy |
| title | Synovial Sarcoma Preclinical Modeling: Integrating Transgenic Mouse Models and Patient-Derived Models for Translational Research |
| title_full | Synovial Sarcoma Preclinical Modeling: Integrating Transgenic Mouse Models and Patient-Derived Models for Translational Research |
| title_fullStr | Synovial Sarcoma Preclinical Modeling: Integrating Transgenic Mouse Models and Patient-Derived Models for Translational Research |
| title_full_unstemmed | Synovial Sarcoma Preclinical Modeling: Integrating Transgenic Mouse Models and Patient-Derived Models for Translational Research |
| title_short | Synovial Sarcoma Preclinical Modeling: Integrating Transgenic Mouse Models and Patient-Derived Models for Translational Research |
| title_sort | synovial sarcoma preclinical modeling integrating transgenic mouse models and patient derived models for translational research |
| topic | synovial sarcoma conditional mouse models patient-derived xenografts (PDX) epigenetic drugs immunotherapy |
| url | https://www.mdpi.com/2072-6694/15/3/588 |
| work_keys_str_mv | AT lorenalanduzzi synovialsarcomapreclinicalmodelingintegratingtransgenicmousemodelsandpatientderivedmodelsfortranslationalresearch AT francescaruzzi synovialsarcomapreclinicalmodelingintegratingtransgenicmousemodelsandpatientderivedmodelsfortranslationalresearch AT pierluigilollini synovialsarcomapreclinicalmodelingintegratingtransgenicmousemodelsandpatientderivedmodelsfortranslationalresearch AT katiascotlandi synovialsarcomapreclinicalmodelingintegratingtransgenicmousemodelsandpatientderivedmodelsfortranslationalresearch |